RUNX3 protein is overexpressed in human epithelial ovarian cancer.
OBJECTIVE
RUNX family genes, including RUNX3, are developmental regulators that are important in human cancers. The purpose of this study was to evaluate expression and oncogenic potential of RUNX3 in ovarian carcinoma.


METHODS
Immunohistochemical staining was performed on 60 malignant, 14 borderline, and 5 normal ovarian specimens. Correlation between RUNX3 expression with tumor histology was performed. RUNX3 expression was evaluated by quantitative real-time polymerase chain reaction (QRT-PCR) in microdissected normal and malignant epithelial ovarian tissues. Cell proliferation and viability studies were performed on cells expressing RUNX3 by lentiviral infection and cells with silenced RUNX3 expression by siRNA.


RESULTS
RUNX3 expression by immunohistochemistry was higher in serous ovarian carcinomas versus normal ovarian epithelium (P<0.001). Immunofluorescent staining confirmed upregulation of cytoplasmic RUNX3 in ovarian cancer cell lines and tissues. QRT-PCR showed higher RUNX3 mRNA expression in microdissected borderline and malignant ovarian tumor tissues compared with the normal ovarian surface epithelial cells (HOSE) (P=0.006 and P=0.023). Forced RUNX3 expression by lentiviral gene delivery in ovarian cancer cells, SKOV3, that initially showed undetectable RUNX3 expression, resulted in increased cell viability (P=0.043). Silencing RUNX3 expression by siRNA transfection into ovarian cancer cells, OVCAR429, initially expressing high levels of endogenous RUNX3 resulted in a decrease in proliferation (P=0.021).


CONCLUSIONS
These results suggest that RUNX3 has a role in cell proliferation and viability in ovarian cancer.
Nevadunsky
Nicole S
NS
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Barbieri
John S
JS
Kwong
Joseph
J
Merritt
Melissa A
MA
Welch
William R
WR
Berkowitz
Ross S
RS
Mok
Samuel C
SC
D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis* / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
D050677:Core Binding Factor Alpha 3 Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C493729:Runx3 protein, human